The present invention relates to a method and apparatus for uniformly mixing sample liquids, reagents or other solutions. In particular, the present invention provides a method for rapidly and uniformly mixing a liquid in a container by generating a sinusoidal mixing action of the container.
Automated microbiology and clinical chemistry analyzers identify the presence of microorganisms and analytes in body fluids such as urine, blood serum, plasma, cerebrospinal fluid, sputum and the like. Automated microbiology and clinical chemistry analyzers improve productivity and enable the clinical laboratory to meet the workload resulting from high-test volume. Automated systems provide faster and more accurate results as well as valuable information to clinicians with regard to the types of antibiotics or medicines that can effectively treat patients diagnosed with infections or diseases. In a fully automated analyzer, many different processes are required to identify microorganisms or analytes and an effective type of antibiotic or medicine. Throughout these processes, patient sample liquids and samples in combination with various liquid reagents and antibiotics, are frequently required to be mixed to a high degree of uniformity producing a demand for high speed, low cost mixers that occupy a minimal amount of space.
Analyzers like those described above perform a variety of analytical processes upon microbiological liquid samples and in most of these, it is critical that a patient""s biological sample, particularly when in a liquid state, be uniformly mixed with analytical reagents or diluents or other liquids or even rehydrated compositions and presented to an analytical module in a uniformly mixed state. In a biochemical analyzer, other liquids like broth may need to be uniformly stirred before being used. Various methods have been implemented to provide a uniform sample solution mixture, including agitation, mixing, ball milling, etc. One popular approach involves using a pipette to alternately aspirate and release a portion of liquid solution within a liquid container. Magnetic mixing, in which a vortex mixing action is introduced into a solution of liquid sample and liquid or non-dissolving reagents, herein called a sample liquid solution, has also been particularly useful in clinical and laboratory devices. Typical of such mixing is disclosed in U.S. Pat. No. 6,382,827 wherein a liquid solution in a liquid container is mixed by causing a freely disposed, spherical mixing member to rapidly oscillate within the solution in a generally circular pattern within the container. The spherical mixing member is caused to rapidly move within the solution by revolving a magnetic field at high speed in a generally circular pattern in proximity to the liquid container. Magnetic forces acting upon the magnetic mixing member cause it to generate a mixing motion within the liquid solution.
Ultrasonic mixing techniques like described in U.S. Pat. No. 4,720,374 employ ultrasonic energy applied from the exterior of the package and coupled into a reaction compartment so that a solid tablet of material within the compartment is dissolved or so that liquids contained therein are uniformly mixed. The container may include an array of sonication-improving projections mounted therein and spaced from each other to provide recirculating channels which communicate with both the tablet-receiving recess and the remainder of the volume of the container such that, in use, the projections act to confine a tableted material within a relatively high ultrasonic energy zone and simultaneously permit a flow of hydrating liquid from the high energy zone through the channels thereby to rapidly effect the dissolution of the tableted material.
U.S. Pat. No. 6,382,827 mixes a liquid solution contained in a liquid container by causing a freely disposed, spherical mixing member to rapidly oscillate within the solution in a generally circular pattern within the container. The spherical mixing member is caused to rapidly move within the solution by revolving a magnetic field at high speed in a generally circular pattern in proximity to the liquid container. Magnetic forces acting upon the magnetic mixing member cause it to generate a mixing motion within the liquid solution.
U.S. Pat. No. 5,824,276 cleans contact lens by applying a solution flow in an oscillatory fashion, so that the lens moves up and down within a container but does not contact the container for an extended time period. The method includes suspending the article in a solution within a container such that the article does not experience substantial or extended contact with the container interior. A predetermined flow of solution is passed into the container, thereby providing an upward force which, in conjunction with the buoyancy force, overcomes the downward gravitational force on the article, when the article is more dense than the solution. Alternatively, if the article has a lower density than the treatment solution, the flow is generated at the top of the container, to produce a substantially steady state effect.
Accordingly, from a study of the different approaches taken in the prior art to the problems encountered with mixing of small volume solutions taken with the challenges of minimizing the physical size of a magnetic mixer, there is a need for an improved approach to the design of a simplified, space-efficient liquid sample and or sample-reagent mixer. In particular, there is a need for a mixer which enables rapid and uniform mixing of liquid solutions contained in one or more wells in a multi-well tray or of liquid solutions contained in tubes held in a sample tube rack without mechanisms to move the tray or tubes to a separate location for mixing. There is a further need for a method for liquid mixing that is of such high speed that multiple mixing processes may be achieved without adversely affecting the time required for liquid solution analysis. There is a even further need for a method for mixing device having a mixing motion that is unidirectional so as to positively affect the cost reduction of liquid solution analysis.
Many of these disadvantages to the prior art are overcome by using the methods of this invention. This invention provides a method for generating a vortex-like mixing action within a liquid held in a container by causing the container to move back and forth in a constant sinusoidal pattern at high speeds. Momentum forces acting upon the liquid solution cause it to generate an internal mixing motion of the liquid solution without the aid of extraneous mixing members. The stroke and frequency may be optimized depending upon the geometrical sizes of the container.